Global TB Drug Resistance Called 'Worrying'

Action Points

Explain that an international study found rates of resistance to second-line anti-tuberculous drugs to be high in a variety of countries which raised the percentage of extensively drug resistant tuberculosis cases (XDR-TB).

Note that previous use of second-line agents was the single, most predictive risk factor for drug resistance to these classes of agents, including fluoroquinolones.

Nearly half of tuberculosis patients studied in eight countries were resistant to at least one second-line drug and some 7% of cases were extensively drug-resistant, researchers said.

The four-continent study also found that previous exposure to second-line drugs was the strongest and most consistent risk factor for resistance to such agents, followed by factors related generally to ill health such as smoking and unemployment, according to Tracy Dalton, PhD, of the CDC in Atlanta, and colleagues.

Writing online in The Lancet, the researchers called the global scale of TB drug resistance "worrying" and called for control efforts to take "social factors" into account.

They also noted that risk factors for drug resistance varied by country, allowing government officials to develop policies and treatment strategies tailored to their individual national situations.

In an accompanying commentary, Sven Hoffner, PhD, of the Swedish Institute for Communicable Disease Control in Solna, Sweden, agreed that the study findings could be valuable in efforts to combat TB.

"Updated information on MDR [multidrug-resistant) tuberculosis and investigation of the trends are urgently needed, especially since the true scale of the burden of MDR and XDR [extensively drug resistant] tuberculosis might be underestimated and seem to be rapidly increasing," he wrote.

Dalton and colleagues are leading an ongoing project called the Preserving Effective TB Treatment Study (PETTS) to monitor the epidemiology of drug-resistant TB.

The current report involved evaluation of 1,278 TB cases in Estonia, Latvia, Russia, South Africa, South Korea, the Philippines, Thailand, and Peru.

Drug susceptibility results, performed in a CDC laboratory, were as follows:

Resistance to at least one second-line drug: 43.7%

Resistance to at least one second-line injectable drug: 20.0%

Resistance to at least one fluoroquinolone: 12.9%

XDR TB (resistance to first-line drugs and at least two second-line agents in different classes): 6.7%

Rates of XDR infection were highest in South Korea, where 15% of the 99 patients evaluated were found to be extensively resistant, and lowest in the Philippines, with a rate of 0.8% among 397 cases.

Patterns of resistance to specific drugs also varied substantially. For example, although rates of XDR disease were similar in Estonia and Latvia, resistance to at least one fluoroquinolone was nearly twice as high in Latvia than in Estonia (26% versus 14% of cases.

Statistical analysis of potential risk factors showed that previous treatment with second- or third-line drugs -- including fluoroquinolones, other oral agents, and injectables considered separately -- was a strong predictor of XDR infection as well as resistance to second-line drugs.

Specifically, risk ratios for XDR disease exceeded 4.0 for each such category of exposure (P<0.0001 for all).

Resistance to injectable second-line drugs was not only more prominent in patients with previous exposures, but also in those with risk factors including history of imprisonment and current unemployment, alcohol abuse, and tobacco use, with risk ratios ranging from 1.60 to 2.08 (all P≤0.0001).

In his commentary, Hoffner said the findings could be directly helpful in national TB control programs.

"Knowledge of the risk factors in specific settings will help to direct the use of new diagnostic tools," he wrote.

One problem, though, is that reliable susceptibility testing for one major first-line drug, pyrazinamide, is "almost totally lacking for areas with a high prevalence of MDR tuberculosis."

Such a test, Hoffner suggested, could help identify patients who might respond to drug combinations that include pyrazinamide.

Limitations to the study that were cited by Dalton and colleagues included variability in data collection methods among study locations and the lack of participation in PETTS by India and China, which numerically have the world's largest TB burdens.

The study was funded by the U.S. Agency for International Development, the CDC, the National Institutes of Health, and the Korean Ministry of Health and Welfare.

All study authors and Hoffner declared they had no relevant financial interests.

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